Healthy
Conditions
Keywords
safety, Pharmacokinetics, Immunogenicity
Brief summary
This study is a Phase 1 Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to compare the PK, safety and immunogenicity of the proposed biosimilar test product CT-P16 with EU-approved Avastin and US-licensed Avastin after a single IV infusion of 5mg/kg of each product to healthy male subjects
Detailed description
This study is a double-blind, three-arm, parallel group, single-dose study. A total of 141 subjects will be enrolled; 47 subjects in each of the 3 arms of the clinical study. In each arm, all subjects will receive a single dose (5 mg/kg) of either CT-P16, EU-approved Avastin, or US-licensed Avastin by intravenous (IV) infusion for 90 min (±5 min) on Day 1 followed by 15 weeks during which the PK, safety, and immunogenicity measurements will be made. The randomization will be stratified by body weight and site.
Interventions
DRUGCT-P16
CT-P16 is a biosimilar product for Avastin
DRUGEU-approved Avastin
EU-approved Avastin
US-licensed Avastin
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects between the ages of 19 and 55 years, both inclusive * Body Mass Index (BMI) between 18.0 and 29.9 kg/m2 (both inclusive) and a body weight ≥ 50 kg
Exclusion criteria
* Subject is a female. * Clinically significant allergic reactions, hypersensitivity * A disease classed as significant by the Investigator * Non-healing wound, ulcer, bone fracture, a major surgical procedure, significant traumatic injury * Any malignancy * Undergone treatment with an investigational drug or participated in another clinical trial * Plans to father a child or donates sperms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-inf | pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI | Area under the concentration-time curve from time zero to infinity |
| Cmax | pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI | Maximum Serum Concentration (Cmax) |
| AUC0-last | pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional Pharmacokinetics (Time to Cmax) | pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI | To assess the additional PK of study drugs (Time to Cmax) |
| Number of Participants With Anti-Drug Antibody Positive | up to 15 weeks | number of participants with anti-drug antibody positive at post-dose |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CT-P16 CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects
CT-P16: CT-P16 is a biosimilar product for Avastin | 46 |
| EU-approved Avastin EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects
EU-approved Avastin: EU-approved Avastin | 47 |
| US-licensed Avastin US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects
US-licensed Avastin: US-licensed Avastin | 48 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | US-licensed Avastin | Total | CT-P16 | EU-approved Avastin |
|---|---|---|---|---|
| Age, Continuous | 26.5 years STANDARD_DEVIATION 6.28 | 27.8 years STANDARD_DEVIATION 7.57 | 28.5 years STANDARD_DEVIATION 8.69 | 28.4 years STANDARD_DEVIATION 7.59 |
| BMI | 23.17 kg/m^2 STANDARD_DEVIATION 2.303 | 23.09 kg/m^2 STANDARD_DEVIATION 2.357 | 22.89 kg/m^2 STANDARD_DEVIATION 2.31 | 23.20 kg/m^2 STANDARD_DEVIATION 2.492 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 48 Participants | 141 Participants | 46 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Korea | 48 participants | 141 participants | 46 participants | 47 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 48 Participants | 141 Participants | 46 Participants | 47 Participants |
| Weight (kg) | 69.54 kg STANDARD_DEVIATION 8.141 | 70.16 kg STANDARD_DEVIATION 8.845 | 69.93 kg STANDARD_DEVIATION 9.073 | 71.01 kg STANDARD_DEVIATION 9.417 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 47 | 0 / 48 |
| other Total, other adverse events | 15 / 46 | 22 / 47 | 17 / 48 |
| serious Total, serious adverse events | 0 / 46 | 0 / 47 | 0 / 48 |
Outcome results
Primary
AUC0-inf
Area under the concentration-time curve from time zero to infinity
Time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P16 | AUC0-inf | 42034.90 h*ug/mL | Standard Deviation 6070.668 |
| EU-approved Avastin | AUC0-inf | 40413.44 h*ug/mL | Standard Deviation 5012.778 |
| US-licensed Avastin | AUC0-inf | 43017.95 h*ug/mL | Standard Deviation 5782.951 |
Primary
AUC0-last
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration
Time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P16 | AUC0-last | 41142.81 h*ug/mL | Standard Deviation 5694.184 |
| EU-approved Avastin | AUC0-last | 39411.98 h*ug/mL | Standard Deviation 4649.319 |
| US-licensed Avastin | AUC0-last | 41804.05 h*ug/mL | Standard Deviation 5463.814 |
Primary
Cmax
Maximum Serum Concentration (Cmax)
Time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P16 | Cmax | 117.22 ug/mL | Standard Deviation 17.756 |
| EU-approved Avastin | Cmax | 114.06 ug/mL | Standard Deviation 15.391 |
| US-licensed Avastin | Cmax | 113.09 ug/mL | Standard Deviation 17.402 |
Secondary
Additional Pharmacokinetics (Time to Cmax)
To assess the additional PK of study drugs (Time to Cmax)
Time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Population: PK population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P16 | Additional Pharmacokinetics (Time to Cmax) | 2.5 h |
| EU-approved Avastin | Additional Pharmacokinetics (Time to Cmax) | 2.5 h |
| US-licensed Avastin | Additional Pharmacokinetics (Time to Cmax) | 2.5 h |
Secondary
Number of Participants With Anti-Drug Antibody Positive
number of participants with anti-drug antibody positive at post-dose
Time frame: up to 15 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P16 | Number of Participants With Anti-Drug Antibody Positive | 2 Participants |
| EU-approved Avastin | Number of Participants With Anti-Drug Antibody Positive | 2 Participants |
| US-licensed Avastin | Number of Participants With Anti-Drug Antibody Positive | 3 Participants |